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1.
Toxicology ; 506: 153865, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38876198

RESUMO

Dry hitting, a phenomenon produced by e-cigarettes with refillable cartridges when the liquid in the coil is low, is a common occurrence among regular vapers despite being an unintended consequence of the device. This phenomenon's hazard to public health is still unknown and needs further investigation. Lung cells cultured at the air-liquid interface were exposed to vaped aerosol consisting of 3 % w/v ethyl maltol in propylene glycol for three-second puffs every 30 seconds for 80 total puffs with either dry hit or saturated conditions. Cytotoxicity was measured colorimetrically. The thermal degradation of the heating coils and wicks was visualized using scanning electron microscopy. The chemical byproducts in the aerosol were analyzed using proton nuclear magnetic resonance and inductively coupled plasma mass spectrometry. The results revealed a highly significant increase in cytotoxicity from dry hit treatments. Imaging showed thermal decomposition of the cotton wick after dry hitting, which was confirmed by energy dispersive x-ray spectroscopy with less oxygen in the dry hit cotton. Chemical byproducts were found via unique peaks in the dry hit condensate in the aromatic and alkene regions. Saturated condensate showed higher concentrations of detected metal species than dry-hit condensate. E-cigarette users should avoid dry hitting by refilling tanks or cartridges preemptively or by using disposable coils to avoid increased toxicity during vaping.


Assuntos
Aerossóis , Sobrevivência Celular , Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Sobrevivência Celular/efeitos dos fármacos , Vaping/efeitos adversos , Pulmão/efeitos dos fármacos
2.
Int J Biol Macromol ; 271(Pt 2): 132603, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38788877

RESUMO

Surface-functionalized cellulose materials are developed for various purposes, including food additives and food contact materials. A new biologically relevant testing strategy has been developed based on guidance from the European Food Safety Authority to demonstrate the safety of several next-generation surface-functionalized cellulose materials. This strategy involves a complex three-stage simulated digestion to compare the health effects of thirteen novel different types of cellulose. The physical and chemical properties of surface-functionalized fibrillated celluloses differed depending on the type, amount, and location of functional groups such as sulfonate, TEMPO-oxidized carboxy, and periodate-chlorite oxidized dicarboxylic acid celluloses. Despite exposure to gastrointestinal fluids, the celluloses maintained their physicochemical properties, such as negative surface charges and high length-to-width/thickness aspect ratios. An established intestinal co-culture model was used to measure cytotoxicity, barrier integrity, oxidative stress, and pro-inflammatory response to create a toxicological profile for these unique materials. We conclude that the C6 carboxylated cellulose nanofibrils by TEMPO-oxidation induced the most toxicity in the biological model used in this study and that the observed effects were most prominent at the 4-hour post-exposure time point.


Assuntos
Celulose , Digestão , Celulose/química , Humanos , Propriedades de Superfície , Trato Gastrointestinal/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Modelos Biológicos , Células CACO-2 , Nanofibras/química
3.
Cell Biol Toxicol ; 40(1): 21, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584208

RESUMO

Environmental contaminants are ubiquitous in the air we breathe and can potentially cause adverse immunological outcomes such as respiratory sensitization, a type of immune-driven allergic response in the lungs. Wood dust, latex, pet dander, oils, fragrances, paints, and glues have all been implicated as possible respiratory sensitizers. With the increased incidence of exposure to chemical mixtures and the rapid production of novel materials, it is paramount that testing regimes accounting for sensitization are incorporated into development cycles. However, no validated assay exists that is universally accepted to measure a substance's respiratory sensitizing potential. The lungs comprise various cell types and regions where sensitization can occur, with the gas-exchange interface being especially important due to implications for overall lung function. As such, an assay that can mimic the alveolar compartment and assess sensitization would be an important advance for inhalation toxicology. Some such models are under development, but in-depth transcriptomic analyses have yet to be reported. Understanding the transcriptome after sensitizer exposure would greatly advance hazard assessment and sustainability. We tested two known sensitizers (i.e., isophorone diisocyanate and ethylenediamine) and two known non-sensitizers (i.e., chlorobenzene and dimethylformamide). RNA sequencing was performed in our in vitro alveolar model, consisting of a 3D co-culture of epithelial, macrophage, and dendritic cells. Sensitizers were readily distinguishable from non-sensitizers by principal component analysis. However, few differentially regulated genes were common across all pair-wise comparisons (i.e., upregulation of genes SOX9, UACA, CCDC88A, FOSL1, KIF20B). While the model utilized in this study can differentiate the sensitizers from the non-sensitizers tested, further studies will be required to robustly identify critical pathways inducing respiratory sensitization.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Transcriptoma/genética , Pulmão , Alérgenos/toxicidade
4.
Toxicology ; 504: 153785, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518839

RESUMO

As environmental air quality worsens and respiratory health injuries and diseases increase, it is essential to enhance our ability to develop better methods to identify potential hazards. One promising approach in emerging toxicology involves the utilization of lung surfactant as a model that addresses the limitations of conventional in vitro toxicology methods by incorporating the biophysical aspect of inhalation. This study employed a constrained drop surfactometer to assess 20 chemicals for potential surfactant inhibition. Of these, eight were identified as inhibiting lung surfactant function: 1-aminoethanol, bovine serum albumin, maleic anhydride, propylene glycol, sodium glycocholate, sodium taurocholate, sodium taurodeoxycholate, and Triton X-100. These results are consistent with previously reported chemical-induced acute lung dysfunction in vivo. The study provides information on each chemical's minimum and maximum surface tension conditions and corresponding relative area and contact angle values. Isotherms and box plots are reported for selected chemicals across doses, and vector plots are used to summarize and compare the results concisely. This lung surfactant bioassay is a promising non-animal model for hazard identification, with broader implications for developing predictive modeling and decision-making tools.


Assuntos
Ensaios de Triagem em Larga Escala , Surfactantes Pulmonares , Ensaios de Triagem em Larga Escala/métodos , Tensão Superficial/efeitos dos fármacos , Animais , Benchmarking , Humanos , Relação Dose-Resposta a Droga
5.
Environ Toxicol Pharmacol ; 106: 104380, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309542

RESUMO

In the environment, organisms are exposed to mixtures of different toxicants, which may interact in ways that are difficult to predict when only considering each component individually. Adapting and expanding tools from pharmacology, the toxicology field uses analytical, graphical, and computational methods to identify and quantify interactions in multi-component mixtures. The two general frameworks are concentration addition, where components have similar modes of action and their effects sum together, or independent action, where components have dissimilar modes of action and do not interact. Other interaction behaviors include synergism and antagonism, where the combined effects are more or less than the additive sum of individual effects. This review covers foundational theory, methods, an in-depth survey of original research from the past 20 years, current trends, and future directions. As humans and ecosystems are exposed to increasingly complex mixtures of environmental contaminants, analyzing mixtures interactions will continue to become a more critical aspect of toxicological research.


Assuntos
Ecossistema , Ecotoxicologia , Humanos , Substâncias Perigosas/toxicidade
6.
Int J Mol Sci ; 24(22)2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-38003318

RESUMO

Parkinson's disease (PD) is a neurodegenerative condition marked by loss of motor coordination and cognitive impairment. According to global estimates, the worldwide prevalence of PD will likely exceed 12 million cases by 2040. PD is primarily associated with genetic factors, while clinically, cases are attributed to idiopathic factors such as environmental or occupational exposure. The heavy metals linked to PD and other neurodegenerative disorders include copper, manganese, and zinc. Chronic exposure to metals induces elevated oxidative stress and disrupts homeostasis, resulting in neuronal death. These metals are suggested to induce idiopathic PD in the literature. This study measures the effects of lethal concentration at 10% cell death (LC10) and lethal concentration at 50% cell death (LC50) concentrations of copper, manganese, and zinc chlorides on SH-SY5Y cells via markers for dopamine, reactive oxygen species (ROS) generation, DNA damage, and mitochondrial dysfunction after a 24 h exposure. These measurements were compared to a known neurotoxin to induce PD, 100 µM 6-hydroxydopamine (6-ODHA). Between the three metal chlorides, zinc was statistically different in all parameters from all other treatments and induced significant dopaminergic loss, DNA damage, and mitochondrial dysfunction. The LC50 of manganese and copper had the most similar response to 6-ODHA in all parameters, while LC10 of manganese and copper responded most like untreated cells. This study suggests that these metal chlorides respond differently from 6-ODHA and each other, suggesting that idiopathic PD utilizes a different mechanism from the classic PD model.


Assuntos
Neuroblastoma , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/metabolismo , Manganês/toxicidade , Cobre/toxicidade , Zinco/toxicidade , Metais , Espécies Reativas de Oxigênio/metabolismo , Intoxicação por Metais Pesados , Linhagem Celular Tumoral , Dopamina
7.
Curr Res Toxicol ; 4: 100101, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36687216

RESUMO

Lung surfactant (LS) is a mixture of lipids and proteins that forms a thin film at the gas-exchange surfaces of the alveoli. The components and ultrastructure of LS contribute to its biophysical and biochemical functions in the respiratory system, most notably the lowering of surface tension to facilitate breathing mechanics. LS inhibition can be caused by metabolic deficiencies or the intrusion of endogenous or exogenous substances. While LS has been sourced from animals or synthesized for clinical therapeutics, the biofluid mixture has also gained recent interest as a biophysical model for inhalation toxicity. Various methods can be used to evaluate LS function quantitatively or qualitatively after exposure to potential toxicants. A narrative review of the recent literature was conducted. Studies focused whether LS was inhibited by various environmental contaminants, nanoparticles, or manufactured products. A review is also conducted on synthetic lung surfactants (SLS), which have emerged as a promising alternative to conventional animal-sourced LS. The intrinsic advantages and recent advances of SLS make a strong case for more widespread usage in LS-based toxicological assays.

8.
Toxicol Res (Camb) ; 11(4): 565-582, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36051665

RESUMO

Humans are regularly exposed to silica nanoparticles in environmental and occupational contexts, and these exposures have been implicated in the onset of adverse health effects. Existing reviews on silica nanoparticle toxicity are few and not comprehensive. There are natural and synthetic sources by which crystalline and amorphous silica nanoparticles are produced. These processes influence physiochemical properties, which are factors that can dictate toxicological effects. Toxicological assessment includes exposure scenario (e.g. environmental, occupational), route of exposure, toxicokinetics, and toxicodynamics. Broader considerations include pathology, risk assessment, regulation, and treatment after injury. This review aims to consolidate the most relevant and up-to-date research in these areas to provide an exhaustive toxicological profile of silica nanoparticles.

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